The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery
Senecavirus A (SVA) is a picornavirus that causes vesicular disease in swine and the only member of the <i>Senecavirus</i> genus. Like in all members of <i>Picornaviridae</i>, the 5′ untranslated region (5’UTR) of SVA contains an internal ribosome entry site (IRES) that initi...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/11/2159 |
| _version_ | 1797508190867292160 |
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| author | Nana Wang Haiwei Wang Jiabao Shi Chen Li Xinran Liu Junhao Fan Chao Sun Craig E. Cameron Hong Qi Li Yu |
| author_facet | Nana Wang Haiwei Wang Jiabao Shi Chen Li Xinran Liu Junhao Fan Chao Sun Craig E. Cameron Hong Qi Li Yu |
| author_sort | Nana Wang |
| collection | DOAJ |
| description | Senecavirus A (SVA) is a picornavirus that causes vesicular disease in swine and the only member of the <i>Senecavirus</i> genus. Like in all members of <i>Picornaviridae</i>, the 5′ untranslated region (5’UTR) of SVA contains an internal ribosome entry site (IRES) that initiates cap-independent translation. For example, the replacement of the IRES of foot-and-mouth disease virus (FMDV) with its relative bovine rhinitis B virus (BRBV) affects the viral translation efficiency and virulence. Structurally, the IRES from SVA resembles that of hepatitis C virus (HCV), a flavivirus. Given the roles of the IRES in cap-independent translation for picornaviruses, we sought to functionally characterize the IRES of this genus by studying chimeric viruses generated by exchanging the native SVA IRES with that of HCV either entirely or individual domains. First, the results showed that a chimeric SVA virus harboring the IRES from HCV, H-SVA, is viable and replicated normally in rodent-derived BHK-21 cells but displays replication defects in porcine-derived ST cells. In the generation of chimeric viruses in which domain-specific elements from SVA were replaced with those of HCV, we identified an essential role for the stem-loop I element for IRES activity and recombinant virus recovery. Furthermore, a series of stem-loop I mutants allowed us to functionally characterize discrete IRES regions and correlate impaired IRES activities, using reporter systems with our inability to recover recombinant viruses in two different cell types. Interestingly, mutant viruses harboring partially defective IRES were viable. However, no discernable replication differences were observed, relative to the wild-type virus, suggesting the cooperation of additional factors, such as intermolecular viral RNA interactions, act in concert in regulating IRES-dependent translation during infection. Altogether, we found that the stem-loop I of SVA is an essential element for IRES-dependent translation activity and viral replication. |
| first_indexed | 2024-03-10T04:58:48Z |
| format | Article |
| id | doaj.art-0ad08b4b486b40b9b691671d0815f6d2 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T04:58:48Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-0ad08b4b486b40b9b691671d0815f6d22023-11-23T01:55:51ZengMDPI AGViruses1999-49152021-10-011311215910.3390/v13112159The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus RecoveryNana Wang0Haiwei Wang1Jiabao Shi2Chen Li3Xinran Liu4Junhao Fan5Chao Sun6Craig E. Cameron7Hong Qi8Li Yu9State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaDepartment of Chemistry, The Pennsylvania State University, University Park, PA 16802, USAState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27516, USAKey Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, School of Environment, Harbin 150090, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaSenecavirus A (SVA) is a picornavirus that causes vesicular disease in swine and the only member of the <i>Senecavirus</i> genus. Like in all members of <i>Picornaviridae</i>, the 5′ untranslated region (5’UTR) of SVA contains an internal ribosome entry site (IRES) that initiates cap-independent translation. For example, the replacement of the IRES of foot-and-mouth disease virus (FMDV) with its relative bovine rhinitis B virus (BRBV) affects the viral translation efficiency and virulence. Structurally, the IRES from SVA resembles that of hepatitis C virus (HCV), a flavivirus. Given the roles of the IRES in cap-independent translation for picornaviruses, we sought to functionally characterize the IRES of this genus by studying chimeric viruses generated by exchanging the native SVA IRES with that of HCV either entirely or individual domains. First, the results showed that a chimeric SVA virus harboring the IRES from HCV, H-SVA, is viable and replicated normally in rodent-derived BHK-21 cells but displays replication defects in porcine-derived ST cells. In the generation of chimeric viruses in which domain-specific elements from SVA were replaced with those of HCV, we identified an essential role for the stem-loop I element for IRES activity and recombinant virus recovery. Furthermore, a series of stem-loop I mutants allowed us to functionally characterize discrete IRES regions and correlate impaired IRES activities, using reporter systems with our inability to recover recombinant viruses in two different cell types. Interestingly, mutant viruses harboring partially defective IRES were viable. However, no discernable replication differences were observed, relative to the wild-type virus, suggesting the cooperation of additional factors, such as intermolecular viral RNA interactions, act in concert in regulating IRES-dependent translation during infection. Altogether, we found that the stem-loop I of SVA is an essential element for IRES-dependent translation activity and viral replication.https://www.mdpi.com/1999-4915/13/11/2159Senecavirus AIRESstem-loop Itranslationviral replicationpicornavirus |
| spellingShingle | Nana Wang Haiwei Wang Jiabao Shi Chen Li Xinran Liu Junhao Fan Chao Sun Craig E. Cameron Hong Qi Li Yu The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery Viruses Senecavirus A IRES stem-loop I translation viral replication picornavirus |
| title | The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery |
| title_full | The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery |
| title_fullStr | The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery |
| title_full_unstemmed | The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery |
| title_short | The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent Translation Activity and Virus Recovery |
| title_sort | stem loop i of senecavirus a ires is essential for cap independent translation activity and virus recovery |
| topic | Senecavirus A IRES stem-loop I translation viral replication picornavirus |
| url | https://www.mdpi.com/1999-4915/13/11/2159 |
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